Metabolism by aldehyde oxidase (AO) has been responsible for a number of drug failures in clinical trials. The main reason is the clearance values for drugs metabolized by AO are underestimated by allometric scaling from preclinical species. Furthermore, in vitro human data also underestimates clearance. We have developed the first in silico models to predict both in vitro and in vivo human intrinsic clearance for 8 drugs with just two chemical descriptors. These models explain a large amount of the variance in the data using two computational estimates of the electronic and steric features of the reaction. The in vivo computational models for human metabolism are better than in vitro preclinical animal testing at predicting human intrinsic clearance. Thus, it appears that AO is amenable to computational prediction of rates, which may be used to guide drug discovery, and predict pharmacokinetics for clinical trials.
Pharmacology, Toxicology and Pharmaceutical Science
9
21%
Medicine and Dentistry
8
19%
Agricultural and Biological Sciences
2
5%
Physics and Astronomy
2
5%
Other
3
7%
Unknown
8
19%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 February 2013.
All research outputs
#18,329,207
of 22,696,971 outputs
Outputs from Molecular Pharmaceutics
#2,762
of 4,069 outputs
Outputs of similar age
#222,707
of 287,582 outputs
Outputs of similar age from Molecular Pharmaceutics
#44
of 66 outputs
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So far Altmetric has tracked 4,069 research outputs from this source. They receive a mean Attention Score of 4.6. This one is in the 4th percentile – i.e., 4% of its peers scored the same or lower than it.
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We're also able to compare this research output to 66 others from the same source and published within six weeks on either side of this one. This one is in the 10th percentile – i.e., 10% of its contemporaries scored the same or lower than it.
